Successful regeneration in the CNS first requires that the neurons survive their axotomy and regrow their axons back into their original innervation territory. Experimental transection of the septal input into the adult rat hippocampal formation results in the death of most of the axotomized septal neurons. Recently, three groups have independently reported that intraventricular infusion of Nerve Growth Factor (NGF) will prevent the death of most of these neurons. Axons from the NGF-rescued cholinergic septal neurons even begin to sprout back toward the denervated hippocampus but they build up on the proximal side of the transection site, apparently finding an unfavorable terrain for continued regeneration beyond it. Past in vitro studies indicate that neurons placed into culture will survive only in the presence of added trophic factors but that separate factors, which do not support neuronal survival by themselves, are required by the trophic factor-supported neurons to regenerate their axons. Several molecules with such "neurite-promoting" activity have been purified from the extracellular matrix. Recently, we have begun to examine an acellular extracellular matrix preparation from human placental amnion membrane as a powerful in vitro substratum for regenerating PNS and CNS axons. Preliminary experiments suggest that this material, implanted in vivo, serves as a "bridge" for regenerating adult rat septal cholinergic axons. The overall aim of this proposal is to use a battery of in vitro and in vivo tests to define and optimize this preparation as a bridging material for CNS regeneration.